22-31869917-T-G

Position:

• chr22-31869917-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242896.3(DEPDC5):​c.3331-673T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,908 control chromosomes in the GnomAD database, including 11,522 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11522 hom., cov: 31)
• Consequence: DEPDC5 NM_001242896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

Genes affected

DEPDC5 (HGNC:18423): (DEP domain containing 5, GATOR1 subcomplex subunit) This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC5	NM_001242896.3	c.3331-673T>G		intron_variant		ENST00000651528.2	NP_001229825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2	c.3331-673T>G		intron_variant			NM_001242896.3	ENSP00000498382	P4

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55366 AN: 151790 Hom.: 11480 Cov.: 31

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55460 AN: 151908 Hom.: 11522 Cov.: 31 AF XY: 0.368 AC XY: 27299 AN XY: 74236

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.338

Alfa AF: 0.277 Hom.: 14364

Bravo AF: 0.378

Asia WGS AF: 0.354 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.64
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1012068; hg19: chr22-32265903;